A blood test can predict how well patients with advanced breast cancer will respond to targeted therapies – before treatment begins, according to new research.
A team from The Institute of Cancer Research, London, used a liquid biopsy to detect the presence of tiny amounts of cancer DNA in the blood – at the start of treatment, and four weeks into the treatment. They compared the levels of this DNA with patients’ outcomes – including how long it took for a cancer to grow, and how well the cancer was responding to treatment.
Monitoring treatment response non-invasively
The findings, published in the journal Clinical Cancer Research, involved analysing blood samples from patients enrolled in the plasmaMATCH trial for circulating tumour DNA (ctDNA) that is released into the bloodstream by cancer cells. The researchers, based at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), saw a strong association between low levels of ctDNA at the start of treatment, and treatment response. A similar association was seen after four weeks – one treatment cycle.
The results show that it is possible to monitor how well treatment is working through a non-invasive blood test, meaning patients who are not responding well could be identified and moved to alternative treatments sooner.
In the study, funded by Breast Cancer Now, Cancer Research UK, and the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR, the team analysed blood samples from 167 people with advanced breast cancer.
The patients were enrolled in the plasmaMATCH trial – a study run by the ICR’s Clinical Trials and Statistics Unit (ICR-CTSU), and funded by Stand Up To Cancer, a joint fundraising campaign from Cancer Research UK and Channel 4.
The team grouped the patients based on their type of breast cancer and the specific mutations in their genes.
The first group consisted of patients whose cancers had an ESR1, HER2, AKT1, AKT or PTEN mutation, and who received targeted treatments matched to those mutations.
The second group consisted of people with triple negative breast cancer and no targetable mutation. These people received a combination of the PARP inhibitor olarparib, and the ATR inhibitor ceralasertib.
Improved outcomes for those with low ctDNA levels
For patients in the second group, low ctDNA levels before treatment began were associated with longer progression-free survival – 10.2 months, compared with 4.4 months.
In this group, the percentage of patients who responded to treatment – either seeing their tumours shrink or disappear – was 40 per cent, for those with low ctDNA levels, compared with 9.7 per cent for those with higher levels.
A similar, but weaker, association was also observed between pre-treatment ctDNA levels and clinical outcomes in the first group.
After just four weeks of treatment, patients in the first group with undetectable ctDNA went on to have particularly good outcomes. Their cancer was kept at bay for 10.6 months, compared with 3.5 months for those whose ctDNA was still detectable.
In this group, 46.2 per cent of the patients who had low levels of ctDNA after four weeks responded to treatment, compared with 7.9 per cent of those whose ctDNA levels remained high.
In the second group, the blood test after four weeks of treatment also showed a strong link between ctDNA levels and patient outcomes. Patients whose ctDNA was no longer detectable had their cancer kept at bay for 12 months, compared with 4.3 months in patients who still had detectable ctDNA. Treatment response was also significantly higher for those with undetectable ctDNA, with 85.7 per cent responding to therapy, versus 11.4 per cent among those with detectable ctDNA.
These results build on earlier findings from the same team in 2020, which showed that liquid biopsies can accurately detect the genomic changes driving someone’s cancer and help match them to targeted treatments.
The researchers now hope to validate their findings in larger studies. Assessing these blood tests in clinical trials has begun for advanced breast cancer, in the SERENA-6 trial led by Professor Nicholas Turner.
'A clear link'
Dr Iseult Browne, Clinical Research Fellow at The Institute of Cancer Research, London, and first author of the study, said:
“By analysing circulating tumour DNA in blood samples from patients with advanced breast cancer, we identified a clear link between these levels, both at the start and after one cycle of treatment, and how well patients responded to therapy. Patients with low or undetectable ctDNA consistently had better outcomes, including longer progression-free survival and higher response rates. These findings support the use of ctDNA as a non-invasive biomarker for predicting outcomes and monitoring treatment response.”
Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, and study lead, said:
“Our study shows that a simple blood test could give us an early and reliable indication of whether treatment is working for people with metastatic breast cancer. By tracking changes in tumour DNA in the blood just a few weeks into treatment, we can begin to identify who is likely to benefit and who may need a different approach sooner. This has the potential to make treatment decisions faster, more personalised and ultimately more effective for people living with metastatic breast cancer.”